1. Field of the Invention
The present invention relates to soft capsules which encapsulate chitosan therein (hereinafter may be referred to as "chitosan soft capsules"). The chitosan soft capsules of the present invention are advantageously used for controlling blood pressure of hypertensives. The present invention also relates to a process for producing the soft capsules.
2. Background Art
Hypertension; in particular, essential hypertension having no underlying disease, induces lethal diseases of organs such as the heart, brain, and kidneys. Therefore, daily control of blood pressure to a normal state is a key to curing diseases induced by hypertension. A variety of antihypertensive drugs have been developed and employed for treating hypertension. However, such drugs induce adverse side effects such as headache, drowsiness, cough, and depression. Therefore, patients taking such drugs during treatment become de-energized or feel weak, and may suffer degraded quality of life (QOL).
Extensive studies have been carried out for reducing blood pressure without use of conventional drugs. One such study is application of chitosan.
Presently it is well known that chitosan has an antihypertensive effect and that hypertension is caused by excess intake of salt. See, for example, OKUDA et al., Journal of Traditional Medicine 11, 198-205, 1994 (Hideo KATO, Tomoko TAGUCHI, Hiromichi OKUDA, Mari KONDO, and Minoru TAKARA).
In the above journal, OKUDA et al. describe that in the digestive tract chitosan captures chloride ions (Cl.sup.-) originating from salt contained in ingested food and excretes the ions into feces, to thereby exhibit an action for reducing blood pressure. Briefly, Cl.sup.- in blood activates an angiotensin-converting enzyme (ACE) which acts to elevate blood pressure, whereas chitosan promotes excretion of chloride ions (Cl.sup.-) into feces, to thereby suppress transfer of Cl.sup.- into blood and reduce blood pressure. A test conducted by OKUDA et al. revealed that intake of chitosan powder in an amount of 5 g per day suppresses human hypertension caused by a high-salt diet.
However, the present inventors have observed that intake of an aqueous solution of cuttlefish-chitosan containing chitosan in an amount as small as 20 mg is effective in reducing blood pressure of hypertensives (see Tests 1 through 5 described below). According to the calculation described by OKUDA et al. the amount of salt captured by 20 mg of chitosan is about 6 mg, and the capture of salt in such a small amount is unlikely to reduce blood pressure. Thus, the present inventors considered that the mechanism of inhibiting Cl.sup.- -intake attributed to chitosan is not a direct capture but involves inhibition of the Cl.sup.- absorption process, such as Cl.sup.- channeling. When channeling-like inhibition occurs, chitosan should manifest its action in an aqueous solution state, and administration of solid state chitosan would provide only poor inhibition efficiency.
In their test, OKUDA et al. administered solid chitosan derived from a crab in an amount as large as 5 g to human subjects. However, daily intake of such a large amount of chitosan from food or drugs is not realistic. As mentioned above, it was previously found that a small amount of chitosan was expected to provide an antihypertensive effect so long as it is used in the form of an aqueous solution. Along this line, studies on preparing an aqueous solution of chitosan have been carried out, and a patent application has been filed (Japanese Patent Laid-Open Publication No.110634/1997).
Briefly, there has been developed a method in which cuttlefish-chitosan having a deacetylation degree of 75% or more is dispersed in an aqueous alkali solution for hydration and an organic acid in an amount of 0.01-5 wt. % is added to the dispersion to thereby form a neutral solution.
In view of the foregoing, the present inventors have conducted a test, in which 1% aqueous solution of cuttlefish-chitosan in a volume of 1-3 ml (equivalent to 10-30 mg of chitosan) was administered to five hypertensive patients, and reduction of blood pressure was observed.
Test for an Effect on Reduction of Blood Pressure Induced by 1% Aqueous Solution of Cuttlefish-Chitosan (pH 5.5-6.0)
Case 1. Age 68, Female
When the subject took 2-3 ml of the cuttlefish-chitosan aqueous solution three times daily, systolic pressure was reduced from 180 mmHg to 150 mmHg. Thereafter, the dose was reduced to 2 ml or less twice daily and the administration was continued. Systolic pressure stabilized at 150 mmHg.
Case 2. Age 72, Male
When the subject took 5 ml of the cuttlefish-chitosan aqueous solution at one dose together with a cup of onion-infused wine, systolic pressure was drastically reduced from 190-200 mmHg to 160 mmHg. The reduction in blood pressure was so drastic that the dose of the solution was reduced to 2 ml and the administration was continued. Thereafter systolic pressure was gradually reduced from 180 mmHg to 170 mmHg and then to 160 mmHg, where it stabilized.
Case 3. Age 57, Male
When the subject took 3 ml cuttlefish-chitosan aqueous solution at one dose together with a cup of black mushroom broth, 2-3 times per day, systolic pressure was reduced from 180 mmHg to about 150 mmHg.
Case 4. Age 51, Male
When the subject took the cuttlefish-chitosan aqueous solution at a dose of 1 ml and five droplets of mixed propolis twice daily, systolic pressure was reduced from 170 mmHg to 150-155 mmHg.
Case 5. Age 46, Female
When the subject took the cuttlefish-chitosan aqueous solution at a dose of 2 ml twice daily, and the administration was continued, systolic pressure was gradually reduced from 150 mmHg to 130-135 mmHg.
In consideration of the above results, application of the cuttlefish chitosan aqueous solution to pharmaceuticals and health food has been studied. However, the cuttlefish-chitosan aqueous solution employs glutamic acid as an organic acid and sodium glutamate, and provides such bad taste that daily intake of the solution as such is difficult. Thus, encapsulation of the solution has also been studied. However, encapsulation of an aqueous solution is difficult in that capsules per se dissolve in water.